We propose to measure the risk of Borrelia spirochete transmission to humans from Ixodes scapularis ticks throughout its geographic range in the U.S. and to develop and validate a spatially explicit risk model based upon vector population density and Borrelia infection prevalence. The density of host-seeking nymphal [. scapularis will be measured by drag sampling of closed-canopy deciduous forest habitats in selected state 9arks or natural areas at 95 locations spaced among 2 degree grid quadrats covering the known species range. Samples of 100 ticks collected from these sites will be assayed by real-time quantitative polymerase chain reaction (RT-PCR) of the 16S rDNA (rrs) gene for identification of genus Borrelia spirochetes. Further characterization of Borrelia spirochetes to subgenospecies levels will be accomplished by RT-PCR with specific DNA probes and nucleotide sequencing. The species, genospecies,and subgenospecies genetic structure of Borrelia spirochetes found in nymphal I. scapularis at each site will be mathematically expressed in terms of relative frequency. The frequency values will be combined with tick density estimates to estimate the risk of human infection at each sample site. Spatial models, employing remotely-sensed environmental data, geographic information systems, and spatial statistics, will be developed to predict risk in unsampled areas and provide a continuous surface map depicting risk throughout the range of/. scapularis. Sampling will be repeated during each of four project years, providing a total of approximately 400 sampling points and an anticipated 5,000 Borrelia genotype determinations. Data from each subsequent year will be used to validate model prediction from previous years, thus accumulating accuracy over the four-year project. The final product will be a surface map of human risk for infection from I. scapularis-borne Borrelia spirochetes for the U.S.